We are analyzing https://link.springer.com/article/10.1007/s12265-014-9605-1.

Title:
Development of Lipoprotein(a) siRNAs for Mechanism of Action Studies in Non-Human Primate Models of Atherosclerosis | Journal of Cardiovascular Translational Research
Description:
Lipoprotein(a) [Lp(a)] has recently been recognized as an independent risk factor for coronary heart disease. While plasma Lp(a) levels are correlated with cardiovascular risk, the mechanism by which this particle contributes to atherosclerosis is largely unknown. Although humanized transgenic mouse model has recently been described to study Lp(a) biology, non-human primates (NHP) are the only preclinical model available that allow study of the role of Lp(a) in atherosclerosis in an innate setting. We describe targeting of LPA using lipid nanoparticle formulated short interfering RNAs (siRNAs) in lean rhesus macaque monkeys. We show >90 % LPA mRNA lowering in the liver and >95 % Lp(a) plasma reduction for over 3 weeks after a single siRNA dose. Given the potency of LPA siRNAs, siRNA approach may enable chronic reduction of Lp(a) in atherosclerotic NHP and help to unmask the role for Lp(a) in the genesis and progression of atherosclerosis in man.
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Keywords {🔍}

article, pubmed, google, scholar, cas, lpa, journal, lipoproteina, atherosclerosis, sirna, research, human, lipoprotein, apolipoproteina, central, plasma, cardiovascular, sirnas, tadinstrapps, disease, apolipoprotein, nature, mice, rna, silencing, development, nonhuman, coronary, transgenic, lipid, access, molecular, usa, privacy, cookies, content, studies, marija, risk, heart, levels, nhp, role, interfering, therapeutics, cholesterol, medicine, tsimikas, marcovina, miller,

Topics {✒️}

month download article/chapter low-density lipoprotein cholesterol lectin-bound plasma fraction extensive atherosclerotic lesions large-scale prospective data vivo anti-hbv activity article tadin-strapps marija tadin-strapps rnai-mediated gene silencing apolipoprotein b-100 particles full article pdf nucleic acids research alpha-cyclodextrin sulfate privacy choices/manage cookies human primate models rna therapeutics provide lauretta le voci merck research labs antisense oligonucleotide directed independent risk factor dgat2 sirna silencing related subjects whhl transgenic rabbits sirna formulation team sirna pm team biophysical research communications major lipid classes lpa gene silencing fatty lesions single sirna dose nasally administered sirna systemically administered sirna potent sirna nanoparticle ccr2-/- mice reveals generating lnp formulations nhp models ldl coronary heart disease european economic area lori andrews satya yendluri rodent myeloid cells guide strand overhangs decreased lesion formation arterial wall influx luciferase clone construct wholly owned subsidiary electronic supplementary material coronary artery disease cholesterol-rich diet combat cardiovascular disease

Questions {❓}

Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?

Schema {🗺️}

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         headline:Development of Lipoprotein(a) siRNAs for Mechanism of Action Studies in Non-Human Primate Models of Atherosclerosis
         description:Lipoprotein(a) [Lp(a)] has recently been recognized as an independent risk factor for coronary heart disease. While plasma Lp(a) levels are correlated with cardiovascular risk, the mechanism by which this particle contributes to atherosclerosis is largely unknown. Although humanized transgenic mouse model has recently been described to study Lp(a) biology, non-human primates (NHP) are the only preclinical model available that allow study of the role of Lp(a) in atherosclerosis in an innate setting. We describe targeting of LPA using lipid nanoparticle formulated short interfering RNAs (siRNAs) in lean rhesus macaque monkeys. We show >90 % LPA mRNA lowering in the liver and >95 % Lp(a) plasma reduction for over 3 weeks after a single siRNA dose. Given the potency of LPA siRNAs, siRNA approach may enable chronic reduction of Lp(a) in atherosclerotic NHP and help to unmask the role for Lp(a) in the genesis and progression of atherosclerosis in man.
         datePublished:2015-01-21T00:00:00Z
         dateModified:2015-01-21T00:00:00Z
         pageStart:44
         pageEnd:53
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            Lp(a)
            NHP models
            LDL-c lowering
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            LNP
            RNAi
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            Human Genetics
            Biomedical Engineering and Bioengineering
            Biomedicine
            general
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      headline:Development of Lipoprotein(a) siRNAs for Mechanism of Action Studies in Non-Human Primate Models of Atherosclerosis
      description:Lipoprotein(a) [Lp(a)] has recently been recognized as an independent risk factor for coronary heart disease. While plasma Lp(a) levels are correlated with cardiovascular risk, the mechanism by which this particle contributes to atherosclerosis is largely unknown. Although humanized transgenic mouse model has recently been described to study Lp(a) biology, non-human primates (NHP) are the only preclinical model available that allow study of the role of Lp(a) in atherosclerosis in an innate setting. We describe targeting of LPA using lipid nanoparticle formulated short interfering RNAs (siRNAs) in lean rhesus macaque monkeys. We show >90 % LPA mRNA lowering in the liver and >95 % Lp(a) plasma reduction for over 3 weeks after a single siRNA dose. Given the potency of LPA siRNAs, siRNA approach may enable chronic reduction of Lp(a) in atherosclerotic NHP and help to unmask the role for Lp(a) in the genesis and progression of atherosclerosis in man.
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      dateModified:2015-01-21T00:00:00Z
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         Lp(a)
         NHP models
         LDL-c lowering
         Atherosclerosis
         siRNA
         LNP
         RNAi
         Cardiology
         Human Genetics
         Biomedical Engineering and Bioengineering
         Biomedicine
         general
         Medicine/Public Health
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            affiliation:
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               type:PostalAddress
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      name:Department of Genetics and Pharmacogenomics, Merck Sharp & Dohme Corp., Boston, USA
      name:Sirna Therapeutics Inc., a Wholly Owned Subsidiary of Merck Sharp & Dohme Corp., San Francisco, USA
      name:Division of Cardiovascular Diseases, Merck Sharp & Dohme Corp., Kenilworth, USA
      name:Sirna Therapeutics Inc., a Wholly Owned Subsidiary of Merck Sharp & Dohme Corp., San Francisco, USA
      name:Sirna Therapeutics Inc., a Wholly Owned Subsidiary of Merck Sharp & Dohme Corp., San Francisco, USA
      name:RNA Therapeutics, Merck Sharp & Dohme Corp., West Point, USA
      name:External Scientific Affairs, Merck Research Labs, Rahway, USA
      name:Division of Cardiovascular Diseases, Merck Sharp & Dohme Corp., Kenilworth, USA
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